Methods and Compositions for Treating Fatty Liver and Viral Infections

Abstract

Methods and compositions for treating fatty liver and viral infections are provided. Aspects of the methods includes administering to a subject in need thereof an effective amount of a KxL motif binding agent, e.g., A27, to treat the subject. Also provided are compositions for use in practicing embodiments of the methods.

1 . A method of treatment, comprising: administering to an individual who has a fatty liver and/or a non-flaviviridae viral infection, a therapeutically effective amount of a compound selected from the group consisting of:
 (a) a compound of Formula I:   
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein:
 X is C or N; 
 Y is C or N; 
 Z 1  is C or N; 
 Z 2  is C or N; 
 R 1  is hydrogen; C 1 -C 6  alkyl; C 1 -C 6  alkyl substituted with a substituted or unsubstituted C 3 -C 8  cycloalkyl, 5-8 membered heterocyclyl, or a 6 membered aryl group; C 2 -C 6  alkenyl; substituted or unsubstituted C 3 -C 8  cycloalkyl, —CO—(C 3 -C 8  cycloalkyl), —CO—(C 1 -C 6  alkyl), —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 6  alkyl), or —SO 2 —(C 3 -C 8  cycloalkyl) group; or R 1  and R 2  together form a 12-25 membered heterocycle, or R 1  and R 5  together form a 12-25 membered heterocycle; 
 L is a bond, —CONH—, —NH—CO—, substituted or unsubstituted C 1 -C 5  alkylene, substituted or unsubstituted C 2 -C 5  heteroalkylene, a substituted or unsubstituted 5 membered heteroaryl group, or a substituted or unsubstituted 5-7 membered heterocyclyl, C 5 -C 7  cycloalkyl, 5-6 membered heteroaryl, or a 6 membered aryl group; or a combination thereof; 
 R 2  is —NH 2 , —NHR′, —NR′R′, —NHCOR′, —NR′COR′, —NHSO 2 R′, —NR′SO 2 R′, —NHSO 2 NH 2 , —NHSO 2 NHR′, —NHC(O)NH 2 , —NHC(O)NHR′, —N(R′)SO 2 NH 2 , —N(R)SO 2 NHR′, —N(R′)C(O)NH 2 , and —N(R′)C(O)NHR′, or a substituted or unsubstituted 5-7 membered heterocyclyl, C 5 -C 7  cycloalkyl, 5-6 membered heteroaryl, or a 6 membered aryl group; 
 R 3 , R 4 , and R 5  are independently hydrogen, halo, —CN, —OH, —OR′, —NH 2 , —NHR′, —NR′R′, —NHCOR′, —NR′COR′, —NHSO 2 R′, —NR′SO 2 R′, —NHSO 2 NH 2 , —NHSO 2 NHR′, —NHC(O)NH 2 , —NHC(O)NHR′, —N(R′)SO 2 NH 2 , —N(R′)SO 2 NHR′, —N(R′)C(O)NH 2 , and N(R)C(O)NHR′, —SO 2 R′, —SO 2 NH 2 , SO 2 NHR′, SO 2 NR′R′, —CONH 2 , —CONHR′, —CONR′R′, —CO 2 H, —CO 2 R′, or a substituted or unsubstituted C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, aryl, heteroaryl, or heterocyclyl group; and 
 R′ is a substituted or unsubstituted C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 8  cycloalkyl, aryl, heteroaryl, or heterocyclyl group, or two R′ groups together with the nitrogen atom to which they are bonded form a heterocyclic ring; 
 
         (b) a compound of Formula II: 
       
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein:
 X is C or N; 
 Y is C or N; 
 R 1  is hydrogen, branched or linear C 1 -C 5  alkyl, C 2 -C 15  alkenyl, unsubstituted or substituted cycloalkyl, —CO-(cycloalkyl), —SO 2 -(cycloalkyl) group, or —(CH 2 ) n —R 11 , or R 5  and R 1  together form a 12-18 membered heterocycle; n is 1 or 2; 
 R 2  is substituted or unsubstituted piperidinyl, 4-pyridyl, pyrrolidinyl, piperazinyl, benzyl, substituted phenyl, or pirazolyl group; 
 R 5  is R 51 R 52 N— or R 54 O—; 
 R 51  is H or substituted or unsubstituted C 1 -C 3  alkyl; R 52  is C 6 -C 8  cycloalkyl, substituted or unsubstituted linear C 1 -C 3  alkyl, or branched C 4 -C 5  alkyl or R 51  and R 52  together with the nitrogen atom to which they are bonded form a 6, 7, 8, or 9-membered heterocyclyl ring containing up to 3 heteroatoms optionally substituted, other than the azaindazole moiety to which it is already attached, by a substituted or unsubstituted benzyl acyl, or sulfonyl group; R 54  is H, substituted or unsubstituted benzyl group, branched C 3 -C 8  alkyl, unsubstituted C 5 -C 8  cycloalkyl, or C 5 -C 8  cycloalkyl substituted with one or more linear or branched C 1 -C 4  alkyl groups; R 11  is C 5 -C 8  cycloalkyl or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
 
         (c) a compound of Formula III: 
       
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein:
 X is C or N; 
 Y is C or N; 
 Z 1  is C or N; 
 Z 2  is C or N; 
 R 1  is hydrogen, branched or linear C 1 -C 5  alkyl, C 2 -C 15  alkenyl, unsubstituted or substituted cycloalkyl, —CO-(cycloalkyl), —SO 2 -(cycloalkyl) group, or —(CH 2 ) n —R 11 , or R 5  and R 1  together form a 12-18 membered heterocycle; n is 1 or 2; 
 R 2  is substituted or unsubstituted phenyl, piperidinyl, 4-pyridyl, pyrrolidinyl, piperazinyl, benzyl, substituted phenyl, or pirazolyl group; R 5  is R 51 R 52 N— or R 54 O—; 
 R 51  is H or substituted or unsubstituted C 1 -C 3  alkyl; R 52  is C 6 -C 8  cycloalkyl, substituted or unsubstituted linear C 1 -C 3  alkyl, or branched C 4 -C 5  alkyl or R 51  and R 52  together with the nitrogen atom to which they are bonded form a 6, 7, 8, or 9-membered heterocyclyl ring containing up to 3 heteroatoms optionally substituted, other than the azaindazole moiety to which it is already attached, by a substituted or unsubstituted benzyl acyl, or sulfonyl group; R 54  is H, substituted or unsubstituted benzyl group, branched C 3 -C 8  alkyl, unsubstituted C 5 -C 8  cycloalkyl, or C 5 -C 8  cycloalkyl substituted with one or more linear or branched C 1 -C 4  alkyl groups; R 1  is C 5 -C 8  cycloalkyl or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
 R 3  and R 5  are independently hydrogen, halo, —CN, —OH, —OR′, —NH 2 , —NHR′, —NR′R′, —NHCOR′, —NR′COR′, —NHSO 2 R′, —NR′SO 2 R′, —NHSO 2 NH 2 , —NHSO 2 NHR′, —NHC(O)NH 2 , —NHC(O)NHR′, —N(R′)SO 2 NH 2 , —N(R′)SO 2 NHR′, —N(R′)C(O)NH 2 , and N(R)C(O)NHR′, —SO 2 R′, —SO 2 NH 2 , SO 2 NHR′, SO 2 NR′R′, —CONH 2 , —CONHR′, —CONR′R′, —CO 2 H, —CO 2 R′, or a substituted or unsubstituted C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, aryl, heteroaryl, or heterocyclyl group; 
 
         (d) a compound of Formula IV: 
       
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein:
 each X is independently selected from C or N; 
 R 1  is absent, hydrogen, (C 1 -C 8 ) alkyl, NR 9 R 10 , halo, amino, —C≡N, (C 2 -C 8 ) alkenyl, (C 2 -C 8 ) alkynyl, (C C 8 ) haloalkyl, (C 2 -C 8 ) haloalkenyl, (C 2 -C 8 ) haloalkynyl, (C 1 -C 8 ) alkoxy, (C 1 -C 8 ) haloalkoxy, (C 1 -C 8 ) alkyl (C 1 -C 6 ) alkoxy, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, CH(O), C(O)OR 8 , SF 5 , —OH, —SH, (C 1 -C 6 ) hydroxyalkyl, (C 1 -C 4 ) alkylsulfonyl, aminosulfonyl, amino (C 1 -C 4 ) alkylsulfonyl or aryl; 
 R 2  is C(O)NR 11 R 12 , C(O)R 13 , 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or 6-membered substituted cycloalkyl; 
 R 3  is H, (C 1 -C 8 ) alkyl, (C 1 -C 8 ) alkenyl, (C 1 -C 8 ) alkynyl, (C 1 -C 8 ) alkoxy, hydroxyl, halo, amino, amido, amino (C 1 -C 8 ) alkylamido, heterocyclyl, sulfonyl, aminosulfonyl, amino (C 1 -C 8 ) alkysulfonyl, cyano, or (C 1 -C 3 ) haloalkyl; 
 each R 4  is independently selected from (C 1 -C 8 ) alkyl, either unsubstituted or substituted with halo, (C 1 -C 8 ) alkoxy, (C 1 -C 8 ) haloaikoxy, S(O)—R 6 , S(O) 2 , S(O) 2 —R 6 , S(O) 2 , C(O)R 6 , C(O)OR 7  or (C 1 -C 8 ) cycloalkyl; or both R 4  together form a (C 1 -C 8 ) cycloalkyl, a (C 1 -C 8 ) substituted cycloalkyl, a (C 1 -C 8 ) heterocycloalkyl, a (C 1 -C 8 ) substituted heterocycloalkyl, a (C 1 -C 8 ) aryl, a (C 1 -C 8 ) substituted aryl, a (C 1 -C 8 ) heteroaryl or a (C 1 -C 8 ) substituted heteroaryl; 
 R 6  is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aminoacyl, substituted aminoacyl, amino, substituted amino, acylamino, substituted acylamino, halo, (C 1 -C 4 ) haloalkyl and cyano; 
 R 7  is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aminoacyl, substituted aminoacyl, amino, substituted amino, acylamino, substituted acylamino, halo, (C 1 -C 4 ) haloalkyl and cyano; 
 R 8  is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aminoacyl, substituted aminoacyl, amino, substituted amino, acylamino, substituted acylamino, halo, (C 1 -C 4 ) haloalkyl and cyano; 
 R 9  is H, (C 1 -C 8 ) alkyl, said (C 1 -C 8 ) alkyl being unsubstituted or substituted with one or more halo; 
 R 10  is H, (C 1 -C 8 ) alkyl, said (C 1 -C 8 ) alkyl being unsubstituted or substituted with one or more halo, or R 9  and R 10 , together with the nitrogen atom to which they are attached, form a 4 or 5 membered nitrogen containing heterocycle, said 4 or 5 membered nitrogen containing heterocycle being unsubstituted or substituted with one or more halo; R is H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, 5-6 membered heterocycle or 5-6 membered heteroaryl; 
 R 11  is selected from H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl; 
 R 12  is selected from H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl; 
 R 11  and R 12 , together with the nitrogen atom to which they are attached, form a 5-8 membered nitrogen containing heterocycle, said 5-8 membered nitrogen containing heterocycle being unsubstituted or substituted with OH, halo, ═O, or (C 1 -C 8 ) alkyl; 
 R 13  is OH, O—(C 1 -C 4 ) alkyl; 
 R 15  is H, (C 1 -C 6 ) alkyl, (C 1 -C) haloalkyl, 4-7 membered heterocycle, 5-6 membered heteroaryl, 3-7 membered cycloalkyl, and wherein each of said 4-7 membered heterocycle, 5-6 membered heteroaryl, 3-7 membered cycloalkyl is unsubstituted or substituted at a substitutable position with one or more ═O, OH, (C 1 -C 8 ) alkyl, (C 1 -C 8 ) haloalkyl, (C 1 -C 8 ) alkoxy, amino, or, (C 1 -C 8 ) aminoalkyl; and 
 R 16  is H, (C 1 -C 8 ) alkyl, or (C 1 -C 8 ) haloalkyl; 
 
         (e) a compound of Formula V: 
       
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein:
 each X is independently selected from C or N; 
 R 1  is absent, hydrogen, (C 1 -C 8 ) alkyl, NR 9 R 10 , halo, amino, —C≡N, (C 2 -C 8 ) alkenyl, (C 2 -C 8 ) alkynyl, (C C 8 ) haloalkyl, (C 2 -C 8 ) haloalkenyl, (C 2 -C 8 ) haloalkynyl, (C 1 -C 8 ) alkoxy, (C 1 -C 8 ) haloalkoxy, (C 1 -C 8 ) alkyl (C 1 -C 6 ) alkoxy, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, CH(O), C(O)OR 8 , SF 5 , —OH, —SH, (C 1 -C 6 ) hydroxyalkyl, (C 1 -C 4 ) alkylsulfonyl, aminosulfonyl, amino (C 1 -C 4 ) alkylsulfonyl or aryl; 
 R 2  is C(O)NR 11 R 12 , C(O)R 13 , 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or 6-membered substituted cycloalkyl; 
 R 3  is H, (C 1 -C 8 ) alkyl, (C 1 -C 8 ) alkenyl, (C 1 -C 8 ) alkynyl, (C 1 -C 8 ) alkoxy, hydroxyl, halo, amino, amido, amino (C 1 -C 8 ) alkylamido, heterocyclyl, sulfonyl, aminosulfonyl, amino (C 1 -C 8 ) alkysulfonyl, cyano, or (C 1 -C 3 ) haloalkyl; 
 each R 4  is independently selected from (C 1 -C 8 ) alkyl, either unsubstituted or substituted with halo, (C 1 -C 8 ) alkoxy, (C 1 -C 8 ) haloaikoxy, S(O)—R 6 , S(O) 2 , S(O) 2 —R 6 , S(O) 2 , C(O)R 6 , C(O)OR 7  or (C 1 -C 8 ) cycloalkyl; or both R 4  together form a (C 1 -C 8 ) cycloalkyl, a (C 1 -C 8 ) substituted cycloalkyl, a (C 1 -C 8 ) heterocycloalkyl, a (C 1 -C 8 ) substituted heterocycloalkyl, a (C 1 -C 8 ) aryl, a (C 1 -C 8 ) substituted aryl, a (C 1 -C 8 ) heteroaryl or a (C 1 -C 8 ) substituted heteroaryl; 
 R 6  is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aminoacyl, substituted aminoacyl, amino, substituted amino, acylamino, substituted acylamino, halo, (C 1 -C 4 ) haloalkyl and cyano; 
 R 7  is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aminoacyl, substituted aminoacyl, amino, substituted amino, acylamino, substituted acylamino, halo, (C 1 -C 4 ) haloalkyl and cyano; 
 R 8  is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, acyl, substituted acyl, carboxyl, alkoxycarbonyl, substituted alkoxycarbonyl, aminoacyl, substituted aminoacyl, amino, substituted amino, acylamino, substituted acylamino, halo, (C 1 -C 4 ) haloalkyl and cyano; 
 R 9  is H, (C 1 -C 8 ) alkyl, said (C 1 -C 8 ) alkyl being unsubstituted or substituted with one or more halo; 
 R 10  is H, (C 1 -C 8 ) alkyl, said (C 1 -C 8 ) alkyl being unsubstituted or substituted with one or more halo, or R 9  and R 10 , together with the nitrogen atom to which they are attached, form a 4 or 5 membered nitrogen containing heterocycle, said 4 or 5 membered nitrogen containing heterocycle being unsubstituted or substituted with one or more halo; R is H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, 5-6 membered heterocycle or 5-6 membered heteroaryl; 
 R 11  is selected from H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl; 
 R 12  is selected from H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl; 
 R 11  and R 12 , together with the nitrogen atom to which they are attached, form a 5-8 membered nitrogen containing heterocycle, said 5-8 membered nitrogen containing heterocycle being unsubstituted or substituted with OH, halo, ═O, or (C 1 -C 8 ) alkyl; 
 R 13  is OH, O—(C 1 -C 4 ) alkyl; 
 R 15  is H, (C 1 -C 6 ) alkyl, (C 1 -C) haloalkyl, 4-7 membered heterocycle, 5-6 membered heteroaryl, 3-7 membered cycloalkyl, and wherein each of said 4-7 membered heterocycle, 5-6 membered heteroaryl, 3-7 membered cycloalkyl is unsubstituted or substituted at a substitutable position with one or more ═O, OH, (C 1 -C 8 ) alkyl, (C 1 -C 8 ) haloalkyl, (C 1 -C 8 ) alkoxy, amino, or, (C 1 -C 8 ) aminoalkyl; and 
 R 16  is H, (C 1 -C 8 ) alkyl, or (C 1 -C 8 ) haloalkyl; and 
 
         (f) a compound of Formula VI: 
       
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein: 
         R 1  is hydrogen; halo, haloalkyl C 1 -C 6  alkyl; C 1 -C 6  alkyl substituted with a substituted or unsubstituted C 3 -C 8  cycloalkyl, 5-8 membered heterocyclyl, or a 6 membered aryl group; C 2 -C 6  alkenyl; substituted or unsubstituted C 3 -C 8  cycloalkyl, —CO—(C 3 -C 8  cycloalkyl), —CO—(C 1 -C 6  alkyl), —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2  (C 1 -C 6  alkyl), or —SO 2 —(C 3 -C 8  cycloalkyl) group; 
         R 2  is C(O)NR 11 R 12 , C(O)R 13 , 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or 6-membered substituted cycloalkyl; 
         R 3  is H, (C 1 -C 8 ) alkyl, (C 1 -C 8 ) alkenyl, (C 1 -C 8 ) alkynyl, (C 1 -C 8 ) alkoxy, hydroxyl, halo, amino, amido, amino (C 1 -C 8 ) alkylamido, heterocyclyl, sulfonyl, aminosulfonyl, amino (C 1 -C 8 ) alkysulfonyl, cyano, or (C 1 -C 3 ) haloalkyl; 
         R 11  is selected from H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl or a alkyl-substituted with one or more of a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl R 12  is selected from H, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl or a alkyl-substituted with one or more of a 5-membered heterocycle, 5-membered substituted heterocycle, 5-membered heteroaryl, 5-membered substituted heteroaryl, 6-membered heterocycle, 6-membered substituted heterocycle, 6-membered heteroaryl, 6-membered substituted heteroaryl, 5-membered cycloalkyl, or 5-membered substituted cycloalkyl, 6-membered cycloalkyl, or a 6-membered substituted cycloalkyl 
         R 11  and R 12 , together with the nitrogen atom to which they are attached, form a 5-8 membered nitrogen containing heterocycle, said 5-8 membered nitrogen containing heterocycle being unsubstituted or substituted with OH, halo, ═O, or (C 1 -C 8 ) alkyl; and 
         R 4  is hydrogen; halo, haloalkyl C 1 -C 6  alkyl; C 1 -C 6  alkyl substituted with a substituted or unsubstituted C 3 -C 8  cycloalkyl, 5-8 membered heterocyclyl, a 5-8 membered aryl, a 5-8 membered heteroaryl, C 2 -C 6  alkenyl; substituted or unsubstituted C 3 -C 8  cycloalkyl, —CO—(C 3 -C 8  cycloalkyl), —CO—(C 1 -C 6  alkyl), —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 6  alkyl), or —SO 2 —(C 3 -C 8  cycloalkyl) group. 
         In some embodiments, R 3  is selected from hydrogen, (C 1 -C 8 ) alkyl, halo or haloalkyl. In some instances, R 3  is hydrogen. In some instances, R 3  is a (C 1 -C 8 ) alkyl, such as methyl, ethyl, propyl, i-propyl, butyl, t-butyl, i-butyl or pentyl. In certain instances, R 3  is methyl. In certain instances, R 3  is t-butyl. In some instances, R 3  is halo, such as fluoro, chloro or bromo. In certain instances, R 3  is fluoro. In some instances, R 3  is a haloalkyl, such as CF 3 , CCl 3  or CBr 3 . In certain instances, R 3  is CF 3 . 
       
     
     
         2 . The method of  claim 1 , wherein the individual has a non-flaviviridae viral infection selected from the group consisting of: an hepadnaviridae virus infection, an alphavirus infection, a coronaviridae infection, a paramyxoviridae infection, and an orthomyxoviridae infection. 
     
     
         3 . The method of  claim 1 , wherein the individual has a hepatitis B virus (HBV), Venezuelan equine encephalitis virus (VEEV), O′nyong nyong virus (ONNV), SARS-CoV-2, Semliki Forest virus (SFV), or chikungunya virus (CHIKV) viral infection. 
     
     
         4 . The method of  claim 1 , wherein the individual has a hepatitis B virus (HBV), Venezuelan equine encephalitis virus (VEEV), SARS-CoV-2, or chikungunya virus (CHIKV) viral infection. 
     
     
         5 . The method of  claim 1 , wherein the compound is co-administered with a second agent. 
     
     
         6 . The method of  claim 2 , wherein the compound is co-administered with a second antiviral agent. 
     
     
         7 . The method of  claim 1 , wherein the compound is administered at a concentration in a range of from at 8 to 100 mg/kg. 
     
     
         8 . The method of  claim 1 , wherein the compound is administered for 3 days or more. 
     
     
         9 . The method of  claim 1 , wherein the compound is A27: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound, or pharmaceutically acceptable salt thereof, selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         11 . The compound, or pharmaceutically acceptable salt thereof, of  claim 10 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         12 . A composition comprising:
 (a) the compound, or pharmaceutically acceptable salt thereof, of  claim 10 ; and   (b) a pharmaceutically acceptable carrier, excipient, or diluent.   
     
     
         13 . The composition of  claim 12 , wherein the composition is a medicament for the treatment of fatty liver and/or a viral infection.